Variant chr19-14950226-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005071.3(SLC1A6):c.1664G>A(p.Arg555Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000766 in 1,436,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

SLC1A6
NM_005071.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

SLC1A6 (HGNC:10944): (solute carrier family 1 member 6) Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC1A6 links:

SLC1A6 (HGNC:):

SLC1A6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13694054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A6	NM_005071.3 linkuse as main transcript	c.1664G>A	p.Arg555Gln	missense_variant	10/10	ENST00000594383.2	NP_005062.1	P48664-1B7Z7Q5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC1A6	ENST00000594383.2 linkuse as main transcript	c.1664G>A	p.Arg555Gln	missense_variant	10/10	2	NM_005071.3	ENSP00000472133.2	P48664-1M0R1V3
SLC1A6	ENST00000221742.7 linkuse as main transcript	c.1664G>A	p.Arg555Gln	missense_variant	9/9	1		ENSP00000221742.3	P48664-1
SLC1A6	ENST00000600144.5 linkuse as main transcript	c.1430G>A	p.Arg477Gln	missense_variant	9/9	1		ENSP00000471038.1	M0R063
SLC1A6	ENST00000430939.6 linkuse as main transcript	c.1472G>A	p.Arg491Gln	missense_variant	9/9	2		ENSP00000409386.2	E7EV13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241296

Hom.:

AF XY:

0.00000766

AC XY:

AN XY:

130596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000345

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000766

AC:

AN:

1436184

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

710062

show subpopulations

Gnomad4 AFR exome

AF:

0.0000608

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000731

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000627

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.1664G>A (p.R555Q) alteration is located in exon 9 (coding exon 9) of the SLC1A6 gene. This alteration results from a G to A substitution at nucleotide position 1664, causing the arginine (R) at amino acid position 555 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0051

T;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.83

T;T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.0

.;N;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.38

N;N;.

REVEL

Benign

0.11

Sift

Benign

0.11

T;T;.

Sift4G

Benign

0.088

T;T;T

Polyphen

0.96

D;P;.

Vest4

0.12

MutPred

0.23

.;Loss of MoRF binding (P = 0.0178);.;

MVP

0.46

MPC

2.5

ClinPred

0.65

GERP RS

5.2

Varity_R

0.091

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over